title: Inhibiting PTEN protects hippocampal neurons against stretch injury by decreasing membrane translocation of AMPA receptor GluR2 subunit.
abstract: The AMPA type of glutamate receptors (AMPARs)-mediated excitotoxicity is involved in the secondary neuronal death following traumatic brain injury (TBI). But the underlying cellular and molecular mechanisms remain unclear. In this study, the role of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in GluR2-lacking AMPARs mediated neuronal death was investigated through an in vitro stretch injury model of neurons. It was indicated that both the mRNA and protein levels of PTEN were increased in cultured hippocampal neurons after stretch injury, which was associated with the decreasing expression of GluR2 subunits on the surface of neuronal membrane. Inhibition of PTEN activity by its inhibitor can promote the survival of neurons through preventing reduction of GluR2 on membrane. Moreover, the effect of inhibiting GluR2-lacking AMPARs was similar to PTEN suppression-mediated neuroprotective effect in stretch injury-induced neuronal death. Further evidence identified that the total GluR2 protein of neurons was not changed in all groups. So inhibition of PTEN or blockage of GluR2-lacking AMPARs may attenuate the death of hippocampal neurons post injury through decreasing the translocation of GluR2 subunit on the membrane effectively.
authors.affiliation: Department of Research Institute of Surgery, Daping Hospital, the Third Military Medical University, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Zai-yun
authors.initials: ZY
authors.lastname: Long
authors.forename: Ya-min
authors.initials: YM
authors.lastname: Wu
authors.forename: Qi
authors.initials: Q
authors.lastname: Wan
authors.forename: Jian-xin
authors.initials: JX
authors.lastname: Jiang
authors.forename: Zheng-guo
authors.initials: ZG
authors.lastname: Wang
mesh_terms: D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000037:antagonists & inhibitors*; D016133:Polymerase Chain Reaction; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D008565:Membrane Proteins; D018091:Receptors, AMPA; D051059:PTEN Phosphohydrolase; C487216:Pten protein, rat; C104722:glutamate receptor ionotropic, AMPA 2